The occurrence of inflammatory respiratory diseases, such as asthma, has increased dramatically in the past decade. This rate of increase is more that can be accounted for by genetic drift alone and suggests a role for the environment. Many hypotheses attempt to explain this phenomenon by citing better hygiene, environmental pollution, viral respiratory tract infections, and/or loss of some protective effect found in a rural lifestyle as culprits in disease initiation and exacerbation. This proposal seeks to determine if exposure during late gestation and/or early neonatal life to respiratory syncytial virus (RSV) infection leads to predisposition, development of, or exacerbation of allergic respiratory disease in the adult. Our hypothesis is that allergic respiratory diseases result, in part, from environmental impact(s) that occur during a critical phase of immuno-maturation. In the short term, this proposal will explore the validity of this hypothesis by accomplishing the following specific aims. Specific Aim #1 is to define the impact of respiratory viral infection on pulmonary pathophysiology of neonatal mice. Specifically, we will address the role of RSV in the initiation of immune changes in the pulmonary microenvironment and determine whether these changes predispose adults to pathologic responses to aeroallergens by addressing the following questions: (A) does neonatal RSV infection predispose adult animals to pathologic responses to allergens or (B) does prior sensitization to allergen prime the neonatal immune system to subsequent RSV infections? Specific Aim #2 is to define the molecular events initiated in response to these environmental insults and realize their links to allergic pulmonary inflammation. The long-term objective of our laboratory is to realize the initiators of the immune and pathophysiological changes that occur during the early stages of pulmonary airways disease and ultimately to understand the fundamental causes of asthma so that more effective interventions and therapy may be developed.